Link between cognitive decline genes and healthy aging

An eight-year-long accrual and analysis of the whole genome sequences of healthy elderly people, or "Wellderly," has revealed a higher-than-normal presence of genetic variants offering protection from cognitive decline, researchers from the Scripps Translational Science Institute (STSI) reported in the journalCell.

The initial findings from the Wellderly Study suggest a possible link between long-term cognitive health and protection from chronic diseases, including cancer, heart disease and diabetes, which account for 90 percent of all deaths in the United States and other industrialized nations and more than 75 percent of health care costs.

"The Wellderly, as we've defined, are exceptional individuals who live into their ninth decade and beyond without developing a significant chronic medical condition," said STSI Director. "Our findings indicate that protection from cognitive decline is associated, not necessarily cause and effect, with healthspan. Since healthspan is woefully understudied, much more work in large numbers of individuals across all ancestries is desperately needed. For this reason, we have made all the genomic data available to the research community and public to help spawn further research."

STSI researchers launched the Wellderly Study in 2007 in hopes of unlocking the genetic secrets behind lifelong health. The ongoing project has enrolled more than 1,400 people from across the country ranging in age from 80 to 105 who have not developed any chronic medical conditions or diseases including cancer, stroke, Alzheimer's, Parkinson's disease, diabetes and heart attack.

John Rawlings, 90, of San Diego is one of the study's participants. The Indiana native and World War II veteran started playing softball in his 70s and was inducted into the National Senior Softball Hall of Fame in 2009. He also is an avid reader.

For the study, researchers sequenced the whole genomes of 600 study participants and compared their DNA with genetic data gathered from 1,507 adults by Inova Translational Medicine Institute as part of a separate study. The ITMI cohort represented the general population. All of the genomes were mapped using the Complete Genomics sequencing platform.

After filtering to control for ethnic differences and blood relatedness, downstream DNA analyses were conducted on the genomes of 511 Wellderly individuals and 686 ITMI individuals. Researchers ended up analyzing 24,205,551 individual gene variants in both groups.

The Wellderly group had a significantly lower genetic risk for Alzheimer's and coronary artery disease, researchers found. However, no difference was found between the two groups in genetic risk for cancer, stroke or type 2 diabetes, suggesting protective behaviors or other genetic characteristics might be at play among the Wellderly.

"We didn't find a silver bullet for healthy longevity," said one of the study's co-authors. "Instead, we found weaker signals among common as well as rare variant sites, which collectively suggest that protection against cognitive decline contributes to healthy aging."

Of particular interest was a group of ultra-rare coding variants found among 10 Wellderly individuals in the COL25A1 gene, which encodes for a major component of amyloid plaques found in the brains of Alzheimer's disease patients. None of the coding variants were found among the ITMI individuals.

"Those gene variants might offer a pathway for the development of new treatments for Alzheimer's," author said.

The initial discoveries around protective factors for Alzheimer's disease and coronary artery disease demonstrate the keys the Wellderly may hold in unlocking ways in which we all may live healthier lives.